Zephyrus I: Evaluation of Efficacy and Safety of Pamrevlumab in Participants With Idiopathic Pulmonary Fibrosis (IPF)
- Registration Number
- NCT03955146
- Lead Sponsor
- FibroGen
- Brief Summary
This is a Phase 3 trial to evaluate the efficacy and safety of 30 milligrams (mg)/kilogram (kg) intravenous (IV) infusions of pamrevlumab administered every 3 weeks as compared to placebo in participants with IPF.
- Detailed Description
This is a Phase 3, randomized, double-blind, placebo-controlled, multi-center trial to evaluate the efficacy and safety of pamrevlumab in participants with IPF.
Participants who are not being treated with approved IPF therapies (that is, nintedanib or pirfenidone) may be eligible for screening. Examples of reasons participants may not be treated with approved IPF therapies include but are not limited to:
* Intolerant or not responsive to approved IPF therapies
* Ineligible to receive these therapies
* Participant voluntarily declines to receive approved IPF therapies after being fully informed of the potential benefits/risks
NOTE: No participant should discontinue an approved IPF therapy for the purpose of enrolling in this study.
The study consists of the following study periods:
* Main (double blind, placebo-controlled) phase:
* Screening period: Up to 6 weeks
* Treatment period: 48 weeks
* Optional, open-label extension (OLE) phase of pamrevlumab:
o Access to pamrevlumab will be available until the last participant completes 48 weeks of treatment in the OLE phase, or pamrevlumab is commercially available for the indication of IPF, or the Sponsor decides to end the OLE phase, whichever occurs first.
* Follow-up period/final safety assessments:
* 28 days after last dose
* 60 days after last dose: follow-up phone call, for a final safety assessment
During the treatment period, co-administration of an approved IPF therapy (that is, pirfenidone or nintedanib) is acceptable if clinically indicated in the Investigator's opinion, provided that the Investigator assesses the potential risks/benefits of combining approved IPF therapies with blinded study treatment.
Participants who discontinue study treatment for any reason should be encouraged to remain in the study and be followed for all study visits and assessments.
Participants who complete the Week 48 visit of the main study (regardless of the number of study drug infusions received) will be eligible to participate in the optional OLE phase of the study that offers continuing access to pamrevlumab regardless of randomization assignment in the main study.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 356
- Diagnosis of IPF as defined by American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japan Radiological Society (JRS)/Latin American Thoracic Association (ALAT) guidelines within the past 7 years prior to study participation.
- High-resolution computed tomography (HRCT) scan at screening, with ≥10% to <50% parenchymal fibrosis (reticulation) and <25% honeycombing.
- FVCpp value >45% and <95% at screening and Day 1 (prior to randomization).
- Diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted and corrected by hemoglobin (Hb) value ≥25% and ≤90% at screening (determined locally).
- Not currently receiving treatment for IPF with an approved therapy (that is, pirfenidone or nintedanib) for any reason, including prior intolerance or lack of response to an approved IPF therapy, or choice to forego treatment with an approved IPF therapy after a full discussion with the Investigator regarding risks/benefits of such therapy.
Key
- Previous exposure to pamrevlumab.
- Evidence of significant obstructive lung disease.
- Female participants who are pregnant or nursing.
- Smoking within 3 months of screening and/or unwilling to avoid smoking throughout the study.
- Interstitial lung disease other than IPF.
- Sustained improvement in the severity of IPF during the 12 months prior to screening.
- History of other types of respiratory diseases including diseases or disorders of the airways, lung parenchyma, pleural space, mediastinum, diaphragm, or chest wall.
- Medical conditions (for example, myocardial infarction [MI]/stroke within the past 6 month), or logistical challenges that in the opinion of the Investigator preclude the participant's adequate participation in the study.
- Acute IPF exacerbation during screening or randomization.
- Use of any investigational drugs or unapproved therapies, or participation in any clinical trial with an investigational new drug within 30 days prior to screening. Or use of approved IPF therapies (that is, pirfenidone or nintedanib) within 1 week prior to screening.
- History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies, or to any component of the excipient.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Main Study Cohort: Placebo Placebo Participants will receive placebo matching to pamrevlumab by IV infusion every 3 weeks for up to 48 weeks in the DB period. Japan Extension Cohort: Placebo Placebo Participants will receive placebo matching to pamrevlumab by IV infusion every 3 weeks for up to 48 weeks. OLE Period: Placebo/Pamrevlumab Pamrevlumab Participants who receive placebo matching to pamrevlumab in the DB period, will receive pamrevlumab 30 mg/kg by IV infusion every 3 weeks for up to 48 weeks in the OLE period or until pamrevlumab is commercially available for the indication of IPF, or the sponsor decides to end the OLE period, whichever occurrs first. Main Study Cohort: Pamrevlumab Pamrevlumab Participants will receive pamrevlumab 30 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion every 3 weeks for up to 48 weeks in the DB period. Japan Extension Cohort: Pamrevlumab Pamrevlumab Participants will receive pamrevlumab 30 mg/kg by IV infusion every 3 weeks for up to 48 weeks. OLE Period: Pamrevlumab/Pamrevlumab Pamrevlumab Participants who receive pamrevlumab in the DB period will continue to receive the same dose of pamrevlumab for up to 48 weeks in the OLE period or until pamrevlumab is commercially available for the indication of IPF, or the sponsor decides to end the OLE period, whichever occurrs first.
- Primary Outcome Measures
Name Time Method DB Period (Main Study Cohort): Change From Baseline in FVC at Week 48 Baseline, Week 48 FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC was the volume of air that could forcibly be blown out after full inspiration in the upright position, measured in liters. Least square (LS) mean and standard error (SE) were calculated using mixed model for repeated measures (MMRM).
DB Period (Japan Extension Cohort): Change From Baseline in FVC at Week 48 Baseline, Week 48 FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC was the volume of air that could forcibly be blown out after full inspiration in the upright position, measured in liters.
- Secondary Outcome Measures
Name Time Method DB Period (Main Study Cohort): Time to Disease Progression Up to Week 48 Time to disease progression was defined as the number of weeks from randomization to either the first occurrence of an absolute ≥10% decline from baseline in percent predicted FVC (FVCpp) or all-cause death, whichever occurred first. Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. Hence, the 'Median Time to Event' is longer than the reported timeframe of 48 weeks.
DB Period (Main Study Cohort): Time to First Occurrence of Any Component of the Clinical Composite Endpoint Up to Week 48 The components of the clinical composite endpoint included acute IPF exacerbation, respiratory hospitalization, or death. Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. Hence, the 'Median Time to Event' is longer than the reported timeframe of 48 weeks.
DB Period (Main Study Cohort and Japan Extension Cohort): Change From Baseline in Quantitative Lung Fibrosis (QLF) Volume at Week 48 Baseline, Week 48 The QLF volume was calculated as QLF = total lung capacity volume multiplied by percentage (%) of quantitative lung fibrosis for fibrosis of the whole lung. LS mean and SE was calculated using MMRM.
DB Period (Main Study Cohort): Time to First Acute IPF Exacerbation Up to Week 48 Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. Hence, the 'Median Time to Event' is longer than the reported timeframe of 48 weeks.
DB Period (Main Study Cohort): Time to All-Cause Mortality Up to Week 48 Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. Hence, the 'Median Time to Event' is longer than the reported timeframe of 48 weeks.
DB Period (Main Study Cohort): Time to First Respiratory Hospitalizations Up to Week 48 Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. Hence, the 'Median Time to Event' is longer than the reported timeframe of 48 weeks.
Trial Locations
- Locations (125)
University of Alabama at Birmingham Hospital
🇺🇸Birmingham, Alabama, United States
Banner University Medical Center - Phoenix
🇺🇸Phoenix, Arizona, United States
Norton Thoracic Institute
🇺🇸Phoenix, Arizona, United States
Pulmonary Associates, PA - Research
🇺🇸Phoenix, Arizona, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
J&L Research
🇺🇸Conway, Arkansas, United States
Loma Linda University Health
🇺🇸Loma Linda, California, United States
David Geffen School of Medicine at UCLA
🇺🇸Los Angeles, California, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
University of California San Diego
🇺🇸San Diego, California, United States
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